Fingolimod, otherwise called FTY720, is an immunosuppressant, which is chemically known as 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol and is represented by Formula I:

Fingolimod hydrochloride is currently available as GILENYA® indicated for the treatment of patients with relapsing forms of multiple sclerosis.
U.S. Pat. No. 5,604,229 (U.S. Pat. No. '229) discloses fingolimod and the process for its preparation. Example 28 discloses a process for fingolimod with phenylethylacetate, compound of Formula II, as starting material.

The reaction involves acylation of compound of Formula II with octanoyl chloride by Friedel Crafts acylation. Friedel-Crafts acylation is one of the most important methods for manufacturing acylated benzene derivatives. The reaction typically utilizes an acylating agent and an electrophilic catalyst such as aluminum chloride, boron trifluoride, or hydrogen fluoride. A substituted benzene for example phenylethylacetate, compound of Formula II, as starting material would allow the acylation to potentially occur at different positions on the benzene ring relative to the substituent group. Consequently, in these cases, the reaction may lead to an undesirable mixture of isomeric products comprising both the compound of Formula III (desired compound) and its corresponding regioisomer a compound of Formula IIIA;

This co-production of the regioisomer is disadvantageous since it is structurally similar to the desired compound. The regioisomer compound of Formula IIIA, when present with the compound of Formula III, is expected to undergo a reaction similar to the compound of Formula III. These reactions, in turn, lead to the formation of regioisomeric impurity in each subsequent step that the compound of Formula III undergoes. These culminate to the detrimental formation of the regioisomeric impurity compound of Formula IA, which is difficult to separate from the desired compound fingolimod.

The process disclosed in U.S. Pat. No. '229 disadvantageously generates a set of corresponding regioisomeric impurities. Regioisomeric impurities reduce the yield of the desired product and often form by-products that substantially increase the difficulty of isolating the desired product in high purity. Here, in contrast, the present invention provides a novel process for the preparation of fingolimod, compound of Formula I, that is advantageously and substantially free of its regioisomeric impurity compound of Formula IA, via compound of Formula IV.
The process of the present invention for the preparation of fingolimod, compound of Formula I comprises hydrolysis of compound of Formula III, containing the regioisomeric impurity IIIA, and separating the resultant reaction mixture to obtain the compound of Formula IV, which is free of its regioisomeric impurity compound of Formula IVA.

The compound of Formula IV which is free of regioisomeric impurity compound of Formula IVA is then re-acetylated to obtain compound of Formula III. The compound of Formula III thus obtained is free of regioisomeric impurity compound of Formula IIIA.
The process of the present invention for the preparation of fingolimod, compound of Formula I provides fingolimod, compound of Formula I, which is substantially free of its regioisomeric impurity compound of Formula IA.